Functional Neurological Disorders in the medical education: An urgent need to fill the gaps.

BACKGROUND: FND is a disabling disease that accounts for 5 to 10% of the reason for consultation in neurology. However, young physicians often say they have little or no training in their management. AIM: The aim of the present study was to assess whether French junior neurologists, psychiatrists and physical and rehabilitation medicine (PRM) specialists received teaching on FND during their medical studies, including the residency, and to evaluate their knowledge and perception of the disorder. METHODS: The survey was distributed by the means of a Google form questionnaire to specialist registrars and young specialists with the help of resident's organizations. RESULTS: 568 respondents from the 3 specialties were included in the study. Most respondents (72.4%) were specialists registrars. Almost half of the respondents (45.5%) answered they never received any teaching on FND, and only 20.5% of them knew the Hoover's sign, a positive sign specific of functional weakness. A large majority of respondents felt they were not sufficiently trained in FND (87.9%), and they did not have sufficient knowledge of these disorders (85.3%). DISCUSSION: Better training would allow clinicians to make a diagnosis earlier, to better explain it to patients, and to limit the costs associated with diagnosis delays. A better training of clinicians about FND would also improve the prognosis of patients, as early diagnosis and good explanation is associated with a better prognosis. CONCLUSION: This survey shows that there is a gap about FND in the training programs in the medical studies and during the specialization training of young doctors in France.

The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis

IntroductionPenile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias.Materials and methodsA cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed.ResultsOur study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival.ConclusionPD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis.

INTRODUCTION: Penile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias. MATERIALS AND METHODS: A cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed. RESULTS: Our study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival. CONCLUSION: PD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

[Dyspnoea and Comorbidity in Lung Cancer-Patients: The Therapy Starts with Taking the Patients History]. / Dyspnoe und Komorbidität beim Lungenkarzinom: Warum die Anamnese so wichtig ist.

AIM: Dyspnoea is a frequent and compromising symptom in patients with advanced and metastatic lung cancer. Exogenous as well as endogenous factors contribute to development of shortness of breath. Knowledge of these influences is essential for effective treatment of this important symptom. In our study, we evaluated the influence of cofactors and comorbidity on development of dyspnoea in lung cancer patients for the purpose of effective therapy of shortness of breath in this target group. METHODS: In this prospective monocentric study, we registered severity of dyspnoea in advanced lung cancer patients using the modified Medical Research Council-Scale (mMRC-scale). Patients' history of COPD and cardiopulmonary comorbidity was recorded using a standardized questionnaire. Moreover, cofactors such as pain or cancer-induced mental stress were documented by visual rating scale. RESULTS: 25 (48,1 %) of 52 recruited lung cancer-patients reported moderate or severe dyspnoea. In logistic regression analysis history of COPD or cardiopulmonary comorbidity, severe pain, airway obstruction or pleural effusion were associated with severe dyspnoea (mMRC-scale ≥ 3). Furthermore, in our study cohort lower cancer level III UICC and absence of metastasis correlated with severe dyspnoea. CONCLUSIONS: Our findings confirm the relevance of dyspnoea in patients with advanced lung cancer. Probability of occurrence is influenced by comorbidity and cofactors. The knowledge of these factors contributes to better understanding of occurrence and treatment of dyspnoea.

[Value of combining biologics with methotrexate for treatment of psoriatic arthritis-questions remain]. / Stellenwert der Kombination von Biologika mit Methotrexat in der Behandlung der Psoriasisarthritis ­ Fragen bleiben offen.

BACKGROUND: Concomitant methotrexate (MTX) improves the therapeutic effect of biologic therapies in rheumatoid arthritis treatment. However, the influence of MTX on biologic therapy in psoriasis arthritis (PsA) has not yet been fully clarified, as data from randomized clinical studies are lacking. So far, it is only known, that PsA patients with inadequate response to MTX or non-steroidal anti-inflammatory drugs alone respond equally well to a subsequent biologic therapy. OBJECTIVES: The aim of this study is to investigate whether MTX-naive patients achieve greater disease improvement with the combination of MTX and a biologic than with biologic monotherapy alone, and whether patients on MTX in whom a biologic therapy is additionally started would worsen if MTX is discontinued. METHODS: The current data situation and its limitations are presented. Furthermore, an investigator-initiated multicenter randomized clinical study in patients with active PsA is introduced (MUST study), which investigates the influence of placebo-controlled MTX combination therapy with the interleukin 12/23 inhibitor ustekinumab (UST) in order to close the existing evidence gap. RESULTS: The primary objective of the study is to demonstrate the non-inferiority of UST monotherapy compared to MTX/UST combination therapy as measured by mean DAS28 values at week 24. Of 196 planned patients, 77 have been included so far. Recruitment is still open. CONCLUSION: The MUST study offers the ideal opportunity to investigate the influence of concomitant MTX in a controlled study design and to assess whether the addition of MTX to UST therapy or its continuation is beneficial for PsA patients.

Epidemiology.

The epidemiology of functional neurologic disorders (FND) is complex and has been hampered over the years by a lack of clear definition, with previous definitions struggling with an uneasy mix of both physical and psychologic components. The recent changes in DSM-5 to a definition based on positive identification of physical symptoms which are incongruent and inconsistent with neurologic disease and the lack of need for any associated psychopathology represent a significant step forward in clarifying the disorder. On this basis, FND account for approximately 6% of neurology outpatient contacts and putative community incidence rates of 4-12 per 100 000 per annum. Comorbid neurologic disease occurs in around 10% of cases. The diagnosis is reliable, with revision rates less than 5%. Of note, this revision rate was consistent prior to the widespread utilization of computed tomography and magnetic resonance imaging. FND symptoms are disabling and associated with significant distress. They are more common in women and have a peak incidence between the ages of 35 and 50; however the presentation is common in men and throughout the lifespan. The issues surrounding case definition, ascertainment, misdiagnosis, and risk factors are discussed in detail.

[The salivary glands during rheumatoid arthritis]. / Les glandes salivaries au cours de la polyarthrite rhumatoïde

Salivary gland lesions were studied in 65 non-selected, confirmed rheumatoid polyarthritis patients. The investigations included a careful clinical study, the Schirmer test, sialography, sequential scintigraphy with Technetium 99, and a histological study of the sublingual glands. Tests were also made for salivary gland anti-epithelium antibodies. The frequency of sialography and scintigraphy anomalies is emphasized. In different degrees, two of of three patients presented anatomical or functional anomalies of the salivary glands. These disturbances were not related to the duration, the functional severity, or the treatment of the disease or to the presence of anti-salivary gland antibodies. On the other hand, there was a clear relation with both the presence of anti-nuclear antibodies and an increase in the serum gammaglobulin levels. The limits of the Gougerot syndrome are discussed and it is proposed that there is a need for a second nosological class grouping the minor scintigraphic and sialographic anomalies related to rheumatoid arthritis that has been suggested by several authors.